DENGUE: RE-PACKAGING OF OVERSEAS EXPERIENCE WITH CROSS-COUNTRY STUDIES

By Dr. P. J. Sharma.

“Dengue is one of the fastest emerging infections and is currently the most rapidly spreading mosquito-borne known viral disease” – WHO (World Health Organisation).

Dengue is an endemic disease and one of the major public health problems in India. During the last five years, the National Vector Borne Disease Control Programme (NVBDCP now re-named as NCVBDC) reported 80,725 cases of dengue per year with a fatality rate of about 0.24% in India. According to the WHO, dengue affects approximately 100-400 million people every year. As per a scientific estimation, the global burden of dengue has increased at least fourfold over the last three decades and 2.5 billion people are now at risk of the disease. An estimated 99 million (95% credible interval 71–137 million) symptomatic dengue infections and 404 million asymptomatic (95% credible interval 304–537 million) infections occur annually in over 100 countries, with 500 000 cases of severe dengue and 20 000 deaths. There is an estimated 9 billion dollar direct & indirect medical cost of Dengue in the world.

Before traditional peak season of Dengue (from June to October) seen in India, monsoon enters first in Kerala State where mosquito breeding spots increases and we notice cases of Dengue, Chikungunya, malaria there first. In 2012, epidemiological studies indicated that Tirunelveli in Tamil Nadu was the epicentre of the Dengue epidemic. Since then, Arunachal Pradesh is also experiencing its epicenter at Pasighat township. During covid-19 period, least cases were recorded, may be due to almost restricted movement of community / fever screening of outsiders at entry gate of district/ State. During 2022, imported cases detected in state capital of our State who arrived here from Uganda and some other part of our country like Benglore, Mumbai.  

Awareness generation regarding this disease is very important. For that, National DENGUE Day is observed on 16th May and July month is observed as Anti Dengue Month in India. This Dengue Prevention Campaign aims to sensitize & mobilize community to take immediate action to reduce eruption of dengue cases, by highlighting the health consequences of dengue and areas that are at higher risk.

Dengue is a viral fever which transmits to humans after the bite of an infected female mosquito of the species Aedes aegypti / Aedes albopictus with a habit of day biting. The incubation period of dengue is usually from 4 to 10 days. Dengue virus (of Flaviviridae family) infections can manifest as a wide clinical spectrum of disease, ranging from “dengue fever” (a self limiting mild febrile illness) to”severe dengue” (dengue haemorrhagic fever – which is characterized by capillary leakage leading to hypovolaemic shock, organ impairment and bleeding complications). However most infections remain asymptomatic or cause a relatively mild systemic illness.

Present guidelines of WHO segregates the clinical course of dengue into three stages, – acute, critical, and recovery. In acute phase, may have positive tourniquet test (following the inflation of cuff of a blood pressure measuring instrument, more than 20 petechiae in a 2.5-cm square patch of skin appears), few may have mild hemorrhage (like epistaxis, gum bleeding) and other symptoms – retro-orbital pain, leukopenia, and thrombocytopenia, maculopapular rash, fever, headache, anorexia, vomiting etc. critical phase appears on 2-7 days. With increased capillary permiabuility, progressive leucopenia, thrombocytopenia and raised hematocrit  with decreased platelet count; some may develop severe Dengue. severe mucosal bleeding, extravascular fluid accumulation, pleural effusion, ascites, abdominal pain, persistent vomiting, hepatomegaly ,lethargy, restlessness are seen. Plasma leakage can lead to “shock” associated with scattered intravascular coagulation and narrowed pulse pressure (<20mmHg). Critical organ dysfunction, severe hemorrhage may occur in rare cases without evidence of plasma leakage or shock. Within 48 hours these may be resolved by proper critical management. Within next 2-3 days, extra-vascular fluid will be re-absorpt during its recovery phase. However, pulmonary edema or congestive heart failure may occur, particularly in case of excessive fluid administration. Earlier this disease was classified as 1. Dengue fever, 2. Dengue hemorraghic fever (DHF) and 3. Dengue shock syndrome(DSS) with somewhat overlapping syndromes of dengue. But recent guideline of WHO has simplified the clinical classification of dengue into only two categories – non-severe dengue and severe dengue.

Few studies suggest that maternal dengue infection (materno-fetal transmission, congenital dengue viral infection) during pregnancy might increase the risk of preterm birth and low birth-weight. Neonates with congenital dengue have had clinical manifestations ranging from fever with thrombocytopenia to pleural effusions, severe hemorrhage, and shock.

Dengue virus strains are of four distinct serotypes — DEN-1, DEN-2, DEN-3 and DEN-4. Each of them has multiple genotypes. The genotype variation can be subtle either in DNA material or the envelope. For example, DENV-1 comes in as many as five genotypes –Asia, South Pacific, Thailand, Malaysia and AM/AF. Type I causes classic dengue fever, type II leads to haemorrhagic fever with shock, dengue III causes fever without shock and dengue IV causes fever without shock or profound shock.

Government of India recommends ELISA (enzyme linked immunosorbent assay) based tests as confirmatory tests to detect Dengue. Dengue NS1 (non-structural protein) antigen can be detected in early stage i.e.: within first week from the onset of fever. It is considered to be more sensitive and specific as compared to antibody-based tests.

It is advisable to test for Dengue Immunoglobulin M (IgM) antibody (serological test) after the first week of disease as NS1 antigen may not be detected. Dengue Immunoglobulin G (IgG) antibody (serological test) may be detected in past infection / convalescence somewhere from few weeks to few months after infection. For diagnosis of secondary infection IgM/IgG antibody ratio is used. RDTs (rapid diagnostic tests) are less sensitive and may give false negative results for which ELISA based methods are preferred.

RTPCR (a Molecular tests) is more specific and sensitive than ELISA based diagnostic methods useful in early stages of the disease i.e., within first seven days of onset. But it is not easily available and need help from higher organizations like ICMR.

During preliminary investigation, CBC (Complete blood count) is done. Decreased leucocyte count, decreased platelet count, increased haematocrit level is seen in dengue. A drop in platelet counts below 1,00,000 per µl, referred to as thrombocytopenia, may be seen, especially in severe dengue. While deciding for platelet therapy, Immature platelet fraction (IPF) may be utilized.

For early diagnosis / prevention of complications like severe haemorrhage and shock which require prompt management; a group / combination of tests may be required which may include blood coagulation profile, blood glucose levels, Liver function test, kidney function test etc.

Currently, there is neither any specific cure / antiviral drug nor any vaccine available for dengue. The clinical management relies on judicious fluid replacement of the severe cases and management of the symptoms through mild pain killers and anti-inflammatory drugs along with other necessary supportive. [Pain management is by acetaminophen (paracetamol). Aspirin and ibuprofen should be avoided.] Advice of a qualified doctor is must. Though some dengue vaccines are entering phase III clinical trials, but none is available commercially at this time to be used by community.

From Public Health Point of view, higher Dengue risk locations are about three to ten times more likely to develop into Large Dengue Clusters, compared to areas with lower mosquito populations of Aedes aegypti.

National Environment Agency of Singapore promoting the concept of ‘B-L-O-C-K’ steps for control of Dengue:  Break up hardened soil / Lift and empty flowerpot plates / Overturn pails and wipe their rims / Change water in vases / Keep roof gutters clear and place Bti insecticide inside.

Ten Controlling Steps:

Based on earlier experience, persistently high Aedes aegypti mosquito population, number of dengue cases and active dengue clusters to be detected before traditional peak dengue season (from June to October) comes.

We need intensive and concerted cohesive community effort to search for and remove stagnant water over a 14-day period, starting from pre-monsoon. The effort will cover two mosquito breeding cycles in frequent interval, helping to reduce the mosquito population / risk of dengue. Need to educate community on common mosquito breeding habitats, ground outreach effort to conduct house visits at dengue cluster areas and areas with high Aedes aegypti mosquito population (with technical input from right authority and lined departments), share dengue prevention skills and thus sustain a high level of awareness & source reduction of mosquito breeding spots to be carried out. 

Modern technology of mobile phone provides scope through innovative app to set alerts on areas with dengue clusters and high Aedes aegypti mosquito population. Community can easily receive these push notifications if they pre-set the location on such app.

Weekly once compulsory removal of accumulated water from coolers and other small containers (plastic containers, buckets, used automobile tyres, water coolers, AC equipment s of Home etc, pet watering containers and flower vases) . Need to continue checks at construction sites, and other uncovered  mosquito breeding habitats like raw rubber latex collection boul of Rubber Plantation, uncovered water tank of buildings.

 Water storage containers should be covered with lids at all times.

Community to wear full sleeves clothes, covering their skin in the transmission (rainy) season.

Use a mosquito net or mosquito repellent while sleeping during the day.

Use aerosol during the day to prevent yourself from mosquito bites.

Scientific Entomological Study.

For future study, the genome sequence of the virus collected from the samples to be compared against the GenBank library which hosts all known dengue virus samples since 1943 to present time.

What Next:

Next generation of infected mosquito of Dengue can spread Dengue as all larvae of such infected mosquito carries germs of Dengue. To break this chain, researcher took help of genetic engineering for developing a biological control method. Recently in our country, ICMR-VCRC (Puducherry) developed two colonies of special female mosquito -“Ae.aegypti (Pud)” [wMel Aedes aegypti (Pud) and wAlbB Aedes aegypti (Pud)], one colony infected with wMel and another colony infected with wAlbB Wolbachia bacteria strains. These special female mosquitoes will mate with males and produce larvae that do not carry Dengue viruses. This will gradually decrease and replace the existing population of dengue (and chikungunya) causing infected mosquitoes. (In future it may address the problem of Zika virus also.)  Such mosquitoes will need to be released in the Dengue endemic local areas every 07 days i.e.: weekly. For this kind of activity, regulatory approval takes time regarding screening the Biosafety of such technology etc.

Wolbachia bacteria naturally occurs in 60% of the insects. The eggs of the vector mosquito Aedes aegypti were injected with the Wolbachia bacteria supplied by Monash University, Australia. When injected with Wolbachia (an endo-symbiotic bacteria), it can effectively control the target viruses inside the cells of the mosquito. [Endosymbiont  phenomenon = endo means inside, biont means give and take relationship]. Thus it inhibits infection and transmission of dengue from the bacteria-hosting mosquitoes.

In 2021, to suppress populations of wild Aedes aegypti mosquitoes (which can carry diseases like zika, dengue, chikungunya and yellow feve) such genetically engineered mosquitoes were released into the environment / air in Florida Keys of the United States. The small-scale field trials of genetically engineered cross-bred carrying Aedes aegypti mosquitoes are already performed in Australia, Brazil, Columbia, Indonesia and Vietnam; whereas large-scale field trials (citywide) performed in Yogyakarta city (Indonesia), Rio de Janeiro (Brazil), and Medellín (Colombia). Success was in a range of 70%-95%.

ICMR-VCRC (Puducherry) is waiting for green signal for staring its pilot project in India to control Dengue. It may bring success against Chikungunya & Zika virus also.

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[NB: Observation of “Anti Dengue Month” during July month in India is a national level awareness campaign being celebrated all over India to call people on stage to pay attention for doable preventive and promotive steps, then take corrective measures for the common mistakes of whole human fraternity for combating the DENGUE. This article by Dr. P. J. Sharmah is a carefully contextualized critique on its probable solution from public health point of view with reference of some overseas experience and cross country studies. The contributor may be reached through the e-mail: [email protected]]

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